Growth-inhibitory and tumor-suppressive functions of p53 depend on its repression of CD44 expression (Cell, 2008, 134:62-73)

報告日期: 2008/10/31
報告時間: 17:10/18:00
報告學生: 簡孝儒
講評老師: 賴明德
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971031-3.pdf

Growth-Inhibitory and Tumor-

Suppressive Functions of p53 Depend

on Its Repression of CD44 Expression

Cell 134, 62–73, July, 2008

 

Speaker:簡孝儒

Commentator:賴明德 教授

Date2007/10/31

Time17:10-18:00

PlaceRoom 602

 

Abstract

CD44 is a transmembrane cell-surface protein. Although it lacks its own signaling domain, it has recently been shown to be essential for the homing and stem cell properties of leukemic stem cells. CD44 has also been found to support anchorage-independent growth in vitro and tumor growth and metastasis in experimental models of solid cancers, whereas it inhibited tumor growth in other models. Thus, the role played by CD44 in tumorigenesis is still unclear. Moreover, the CD44 cell-surface antigen serves as a useful marker for detecting and enriching for several types of tumor-initiating cells which is consistent with its tumor-promoting capabilities. The p53 tumor suppressor is a key mediator of cellular responses to various stresses. Most studies of p53 have suggested that the loss of p53 function enables cancer cells to escape p53-induced cytostasis and/or apoptosis. Since the expression of p53 protein in tumor samples indicates the presence of a mutant, functionally inactive p53 protein, this suggested that CD44 might be repressed by wild-type p53. Therefore, the authors hypothesized that signals repressing CD44 expression are essential for growth-inhibitory and tumor- suppressive functions of p53 in tumor progression. Their results indicate that CD44 is a key tumor-promoting agent in transformed tumor cells lacking p53 function. In the absence of p53 function, the resulting derepressed CD44 expression is essential for the growth and tumor-initiating ability of highly tumorigenic mammary epithelial cells. The present results suggested another important benefit conferred on cancer cells by p53 loss—an increased resistance to apoptosis and responsiveness to mitogenic signals resulting from elevated CD44 levels.

 

Reference

1. Helmut Ponta, Larry Sherman and Peter A. Herrlich. CD44: from adhesion molecules to signalling regulators. Mol cell biol 4, 33-45, 2003

2. Levine, A.J. p53, the cellular gatekeeper for growth and division. Cell 88, 323-331.